Acetonitrile → 1-Cyclopropyl-7-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-6,8-difluoro-4-oxo-quinoline-3-carboxylic acid

HRID 483293ノート

反応式

HRID 483293 の反応式
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:16])=[C:11](F)[C:12]=3[F:14])[C:7](=[O:17])[C:6]([C:18]([O:20]C)=[O:19])=[CH:5]2)[CH2:3][CH2:2]1.I[Si](C)(C)C.Br.Br.[CH:29]12[CH2:35][CH:32]([NH:33][CH2:34]1)[CH2:31][NH:30]2.C(#N)C>ClCCl>[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:16])=[C:11]([N:30]4[CH2:31][CH:32]5[CH2:35][CH:29]4[CH2:34][NH:33]5)[C:12]=3[F:14])[C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5]2)[CH2:2][CH2:3]1

参加物

6

反応物 4

HCID 6342AcetonitrileHCID 85247Trimethylsilyl iodide2 回HCID 13590045Methyl 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylateHCID 162131472,5-Diazabicyclo[2.2.1]heptane dihydrobromide

生成物 1

HCID 4695551-Cyclopropyl-7-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-6,8-difluoro-4-oxo-quinoline-3-carboxylic acid収率 92%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 1.0 g (3.4 mmole) of methyl 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate in 25 ml dichloromethane was added 0.6 ml (0.8 g, 4.2 mmole) of iodotrimethylsilane while stirring at room temperature under a blanket of nitrogen. The reaction was warmed to reflux and stirred overnight. An additional 0.23 ml (1.6 mmole) of iodotrimethylsilane was added and the solution was refluxed for another two hours, cooled to room temperature, and concentrated. The residue was taken up in 20 ml of acetonitrile. To this solution was added a mixture of 2.2 g (8.5 mmole) of 2,5-diazabicyclo[2.2.1]heptane, dihydrobromide, 2.7 g (17.9 mmole) 1,8-diazobicyclo[5.4.0]undec-7-ene and 20 ml acetonitrile. The reaction was refluxed for 2.5 hours then cooled to room temperature. The formed precipitate was filtered, washed with acetonitrile and ethyl ether, yielding 1.13 g (92%) of the title compound, mp 288°-290° C.

後処理

  1. temperatureThe reaction was warmed
  2. temperatureto reflux
  3. stirringstirred overnight
  4. temperaturethe solution was refluxed for another two hours
  5. temperaturecooled to room temperature
  6. concentrationconcentrated
  7. additionTo this solution was added
  8. temperatureThe reaction was refluxed for 2.5 hours
  9. temperaturethen cooled to room temperature
  10. filtrationThe formed precipitate was filtered
  11. washwashed with acetonitrile and ethyl ether

出典と根拠

ORDレコード
ord-b9ba5e88e1da40d784731fb8887f0ffe
出典データセット
uspto-grants-1986_03
特許番号
US04578473

反応ノート

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